Chloroform

67-66-3

Hazard Summary-Created in April 1992; Revised in January 2000

Chloroform may be released to the air as a result of its formation in
the chlorination of drinking water, wastewater and swimming pools.
Other sources include pulp and paper mills, hazardous waste sites, and
sanitary landfills. The major effect from acute (short-term) inhalation
exposure to chloroform is central nervous system depression. Chronic
(long-term) exposure to chloroform by inhalation in humans has resulted
in effects on the liver, including hepatitis and jaundice, and
central nervous system effects, such as depression and irritability.
Chloroform has been shown to becarcinogenic in animals after oral
exposure, resulting in an increase in kidney and liver tumors. EPA
has classified chloroform as a Group B2, probable human carcinogen.

Uses

The vast majority of the chloroform produced in the United States
is used to make HCFC-22. The rest is produced for export and for miscellaneous
uses. (1)

Chloroform was used in the past as an extraction solvent for fats,
oils, greases, and other products; as a dry cleaning spot remover; in
fire extinguishers; as a fumigant; and as an anesthetic. However, chloroform
is no longer used in these products. (1)

Sources and Potential Exposure

Chloroform may be released to the air from a large number of sources
related to its manufacture and use, as well as its formation in the
chlorination of drinking water, wastewater, and swimming pools. Pulp
and paper mills, hazardous waste sites, and sanitary landfills are also
sources of air emissions. The background level of chloroform in ambient
air in the early 1990s was estimated at 0.00004 parts per million (ppm).
(1)

Human exposure to chloroform may occur through drinking water, where
chloroform is formed as a result of the chlorination of naturally occurring
organic materials found in raw water supplies. Measurements of chloroform
in drinking water during the 1970s and 1980s ranged from 0.022 to 0.068
ppm. (1)

Chloroform may also be found in some foods and beverages, largely
from the use of tap water during production processes. (1)

Assessing Personal Exposure

Chloroform can be detected in blood, urine, and body tissues. However,
these methods are not very reliable because chloroform is rapidly eliminated
from the body, and the tests are not specific for chloroform. (1)

Health Hazard Information

Acute Effects:

The major effect from acute inhalation exposure to chloroform in
humans is central nervous system depression. At very high levels (40,000
ppm), chloroform exposure may result in death, with concentrations in
the range of 1,500 to 30,000 ppm producing anesthesia, and lower concentrations
(<1,500 ppm) resulting in dizziness, headache, tiredness, and other
effects. (1,2)

Effects noted in humans exposed to chloroform via anesthesia include
changes in respiratory rate, cardiac effects, gastrointestinal effects,
such as nausea and vomiting, and effects on the liver and kidney. Chloroform
is not currently used as a surgical anesthetic. (1,2)

In humans, a fatal oral dose of chloroform may be as low as 10 mL
(14.8 g), with death due to respiratory or cardiac arrest. (1,2)

Chronic exposure to chloroform by inhalation in humans is associated
with effects on the liver, including hepatitis and jaundice, and central
nervous system effects, such as depression and irritability. Inhalation
exposures of animals have also resulted in effects on the kidney. (1,2)

Chronic oral exposure to chloroform in humans has resulted in effects
on the blood, liver, and kidney. (1,2)

EPA has not established a Reference Concentration (RfC)
for chloroform. (4)

The California Environmental Protection Agency
(CalEPA) has established a chronic reference exposure level of 0.3 milligrams
per cubic meter (mg/m3) for chloroform based on exposures
resulting in kidney and liver effects in rats. The CalEPA reference
exposure level is a concentration at or below which adverse health effects
are not likely to occur. It is not a direct estimator of risk,
but rather a reference point to gauge the potential effects. At lifetime
exposures increasingly greater than the reference exposure level, the
potential for adverse health effects increases. (5)

ATSDR has established an acute inhalation minimal risk level (MRL)
of 0.5 mg/m3 (0.1 ppm) based on exposures resulting in liver
effects in mice, an intermediate inhalation MRL of 0.2 mg/m3
(0.05 ppm) based on worker exposures resulting in liver effects in humans,
and a chronic inhalation MRL of 0.1 mg/m3 (0.02 ppm) also
based on liver effects in humans. The MRL is an estimate of the daily
human exposure to a hazardous substance that is likely to be without
appreciable risk of adverse noncancer health effects over a specified
duration of exposure. (1)

The Reference Dose (RfD)
for chloroform is 0.01 milligrams per kilogram per day (mg/kg/d) based
on exposures resulting in fatty cyst formation in the livers of dogs.
The RfD is an estimate (with
uncertainty spanning perhaps an order of magnitude) of a daily oral
exposure to the human population (including sensitive subgroups) that
is likely to be without appreciable risk of deleterious noncancer effects
during a lifetime. (4)

EPA has medium to low confidence in the RfD
due to: medium confidence in the critical study on which the RfD
was based because only two treatment doses were used, and a no-observed-effect
level (NOEL) was not determined;
and medium to low confidence in the database because several studies
support the choice of a lowest-observed-adverse-effect level (LOAEL),
but a NOEL was not found.
(4)

Reproductive/Developmental Effects:

Little information is available on the reproductive or developmental
effects of chloroform in humans, via any route of exposure. A possible
association between certain birth outcomes (e.g., low birth weight,
cleft palate) and consumption of contaminated drinking water was reported.
However, because multiple contaminants were present, the role of chloroform
is unclear. (1)

Reproductive effects, such as decreased conception rates, decreased
ability to maintain pregnancy, and an increase in the percentage of
abnormal sperm were observed in animals exposed to chloroform through
inhalation. (1)

No information is available regarding cancer in humans or animals
after inhalation exposure to chloroform. (1)

Epidemiologic studies suggest an association between cancer of the
large intestine, rectum, and/or bladder and the constituents of chlorinated
drinking water, including chloroform. However, there are no epidemiologic
studies of water containing only chloroform. (1)

Chloroform has been shown to be carcinogenic in animals after oral
exposure, resulting in an increase in kidney and liver tumors. (1)

EPA considers chloroform to be a probable human carcinogen and has
ranked it in EPA's Group B2. (4)

EPA has determined that although chloroform is likely to be carcinogenic
to humans by all routes of exposure under high-exposure conditions that
lead to cell death and regrowth in susceptible tissues, chloroform is
not likely to cause cancer in humans by any route of exposure under
exposure conditions that do not cause cell death and regrowth. Therefore,
EPA has not derived either an oral carcinogenic potency slope or an
inhalation unit risk for chloroform.

Physical Properties

Chloroform is a colorless liquid that is not very soluble in water
and is very volatile. (1,6)

Chloroform has a pleasant, nonirritating odor; the odor threshold
is 85 ppm. (1)

The chemical formula for chloroform is CHCl3, and it has
a molecular weight of 119.38 g/mol. (1)

The vapor pressure for chloroform is 159 mm Hg at 20 °C, and
it has a log octanol/water partition coefficient (log Kow)
of 1.97. (1)

Health Data from Inhalation Exposure

ACGIH TLV--American Conference of Governmental and Industrial
Hygienists' threshold limit value expressed as a time-weighted average;
the concentration of a substance to which most workers can be exposed
without adverse effects. LC50 (Lethal Concentration50)--A calculated
concentration of a chemical in air to which exposure for a specific length
of time is expected to cause death in 50% of a defined experimental animal
population. NIOSH REL--National Institute of Occupational Safety and Health's
recommended exposure limit; NIOSH-recommended exposure limit for an 8-
or 10-h time-weighted-average exposure and/or ceiling. OSHA PEL--Occupational Safety and Health Administration's permissible
exposure limit expressed as a time-weighted average; the concentration
of a substance to which most workers can be exposed without adverse effect
averaged over a normal 8-h workday or a 40-h workweek.

The health and regulatory values cited in this factsheet were obtained
in December 1999.aHealth numbers are toxicological numbers from
animal testing or risk assessment values developed by EPA. b Regulatory numbers are values that have been
incorporated in Government regulations, while advisory numbers are nonregulatory
values provided by the Government or other groups as advice. OSHA
numbers are regulatory, whereas NIOSH and ACGIH numbers are advisory.
cThese cancer risk estimates were derived from
oral data and converted to provide the estimated inhalation risk. dThe LOAEL is from the critical study used
as the basis for the CalEPA chronic reference exposure level.

National Institute for Occupational Safety and
Health (NIOSH). Pocket
Guide to Chemical Hazards. U.S. Department of Health and Human
Services, Public Health Service, Centers for Disease Control and Prevention.
Cincinnati, OH. 1997.